Creating Clinical Trial Readiness for cAMP-Related Dystonias through Natural History Characterization and Therapeutic Discovery

Dr. Ebrahimi-Fakhari’s research will study cAMP-related dystonias and how rare and severe childhood movement disorders are caused by genetic changes that disrupt communication between brain cells. Affected children experience uncontrolled movements, painful muscle contractions, and severe dystonic episodes, yet there are currently no disease-modifying treatments and few therapeutic options. This project will follow 100 children over two years to better understand how these conditions progress and to identify meaningful measures needed for future clinical trials. In parallel, researchers will create patient-derived brain cell models to study disease mechanisms and screen thousands of existing FDA-approved drugs to identify potential treatment candidates.

Integrative Transcriptomic and Machine Learning Framework for Novel Dystonia Gene Identification

Dr. Sarmiento researches how dystonia is a rare movement disorder that causes involuntary muscle contractions and abnormal postures, yet about 80% of cases still lack a known genetic cause. This project will use advanced computational and machine learning approaches to analyze brain gene-expression data and identify new genes that may contribute to dystonia. Researchers will then examine large whole-genome datasets from children with dystonia to find rare, potentially harmful genetic variants in these candidate genes. The goal is to improve genetic diagnosis, better understand disease mechanisms, and support the development of targeted therapies for affected children.

Predictive Modeling of Dystonic Biomarkers Using Minimally Invasive EEG Recordings

Dystonia is a common movement disorder characterized by involuntary muscle contractions and abnormal postures, but its causes and early detection remain poorly understood. This project studies early brain changes using a mouse model in which some animals develop dystonia while others with the same mutation remain symptom-free. Researchers will record brain activity using electroencephalography (EEG) and track movement over time to identify patterns that predict when dystonia symptoms will appear. The goal is to discover early brain markers that could help doctors detect dystonia sooner and guide more effective treatments.

Autophagic Targeting of Nuclear Condensates to Restore Protein Homeostasis in Dystonia

DYT1 dystonia is a childhood-onset movement disorder caused by mutations in the torsin protein, which disrupts how cells maintain healthy proteins. This research found that cells lacking torsin form harmful protein clusters, called condensates, that trap important quality-control factors and lead to cellular stress. Building on previous discoveries, this project will test how activating autophagy—the cell’s natural cleanup system—can remove these toxic condensates and restore normal protein balance. The work aims to identify new therapeutic targets and potential treatment strategies for dystonia.